Acrolein stimulates eicosanoid release from bovine airway epithelial cells

CRAIG A., AND GEORGE D. LEIKAUF. Acrolein stimulates eicosanoid release from bovine airway epithelial cells. Am. J. Physiol. 259 (Lung Cell. Mol. Physiol. 3): L222-L229, 1990.-Injury to the airway mucosa after exposure to environ- mental irritants is associated with pulmonary inflammation and bronchial hyperresponsiveness. To better understand the relationships between mediator release and airway epithelial cell injury during irritant exposures, we studied the effects of acrolein, a low-molecular-weight aldehyde found in cigarette smoke, on arachidonic acid metabolism in cultured bovine tracheal epithelial cells. Confluent airway epithelial cell mono- layers, prelabeled with [“Hjarachidonic acid, released signifi- cant levels of 3H activity when exposed (20 min) to 100 PM acrolein. [3H]arachidonic acid products were resolved using reverse-phase high-performance liquid chromatography. Under control conditions the released 3H activity coeluted predomi- nantly with the cyclooxygenase product, prostaglandin (PG) EP. After exposure to acrolein, significant “peaks” in 3H activity coeluted with the lipoxygenase products 12-hydroxyeicosate- traenoic acid (HETE) and SHETE, as well as with PGE2, PGF2,, and 6-keto-PGF1,. Dose-response relationships for ac- rolein-induced release of immunoreactive PGF2, and PGE2 from unlabeled epithelial monolayers demonstrated 30 PM acrolein as the threshold dose, with 100 PM acrolein inducing nearly a fivefold increase in both PGF2, and PGE*. Cellular viability after exposure to 100 PM acrolein, determined by released lactate dehydrogenase activity, was not affected until exposure periods were ~2 h. These results implicate the airway epithelial cell as a possible source of eicosanoids after exposure to acrolein. arachidonic acid; cigarette smoke; cyclooxygenase; cytotoxicity; lactate dehydrogenase; lipoxygenase; phospholipase AZ; pros- taglandins; trachea LINING THE CONDUCTING AIRWAYS